Hypoxic adipose mesenchymal stem cells derived conditioned medium protects myocardial infarct in rat

摘要

OBJECTIVE: The aim of this study was to explore the impact of normoxic and hypoxic cell-culture conditions on the expression and secretion of adipose mesenchymal stem cells (ADMSCs)-derived paracrine molecules, and to evaluate the cardioprotective role of hypoxic condition medium (hypoCM) in vivo. MATERIALS AND METHODS: Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses of normoxic and hypoxic ADMSCs and their conditioned medium fractions. Then, the effect of hypoCM on cardiomyocytes proliferation and migration was assessed. Moreover, a rat model of myocardial infarct (MI) was established to test the therapeutic effect of hypoCM in vivo. RESULTS: ADMSCs expressed and secreted significantly higher amounts of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and stromal derived factor-1 (SDF-1 or CXCL12) under hypoxic conditions. Furthermore, compared with the vehicle control, hypoCM significantly enhanced the proliferation and migration of cardiomyocytes. Consistent with the in vitro data, hypoCM decreased the infarct size, apoptosis index and apoptosis related protein in the rat MI model. CONCLUSIONS: These findings suggest that ADMSCs promote rat MI via hypoxia-enhanced paracrine.